Skip to main content
SpringerLink
Log in

The Role of Aquaporin Water Channels in Fluid Secretion by the Exocrine Pancreas

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

The mammalian exocrine pancreas secretes a near-isosmotic fluid over a wide osmolarity range. The role of aquaporin (AQP) water channels in this process is now becoming clearer. AQP8 water channels, which were initially cloned from rat pancreas, are expressed at the apical membrane of pancreatic acinar cells and contribute to their osmotic permeability. However, the acinar cells secrete relatively little fluid and there is no obvious defect in pancreatic function in AQP8 knockout mice. Most of the fluid secreted by the pancreas is generated by ductal epithelial cells, which comprise only a small fraction of the gland mass. In the human pancreas, secretion occurs mainly in the intercalated ducts, where the epithelial cells express abundant AQP1 and AQP5 at the apical membrane and AQP1 alone at the basolateral membrane. In the rat and mouse, fluid secretion occurs mainly in the interlobular ducts where AQP1 and AQP5 are again co-localized at the apical membrane but appear to be expressed at relatively low levels. Nonetheless, the transepithelial osmotic permeability of rat interlobular ducts is sufficient to support near-isosmotic fluid secretion at observed rates. Furthermore, apical, but not basolateral, application of Hg2+ significantly reduces the transepithelial osmotic permeability, suggesting that apical AQP1 and AQP5 may contribute significantly to fluid secretion. The apparently normal fluid output of the pancreas in AQP1 knockout mice may reflect the presence of AQP5 at the apical membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig 1.
Fig 2.
Fig 3.
Fig 4.
Fig 5.
Fig 6.

Similar content being viewed by others

References

  • Argent B.E., Arkle S., Cullen M.J., Green R.. 1986. Morphological, biochemical and secretory studies on rat pancreatic ducts maintained in tissue culture. Quart. J. Exp. Physiol. 71:633–648

    CAS  Google Scholar 

  • Bonting S.L., De Pont J.J.H.H.M., Fleuren-Jakobs A.M.M., Jansen J.W.C.M. 1980. The reflexion coefficient as a measure of transepithelial permeability in the isolated rabbit pancreas. J. Physiol. 309:547–555

    PubMed  CAS  Google Scholar 

  • Burghardt B., Elkjær M.L., Kwon T.H., Rácz G.Z., Varga G., Steward M.C., Nielsen S. 2003. Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of human pancreas. Gut 52:1008–1016

    Article  PubMed  CAS  Google Scholar 

  • Case, R.M. 2006. Is the rat pancreas an appropriate model of the human pancreas? Pancreatology 16:180–190

    Article  Google Scholar 

  • Case R.M., Argent B.E. 1993. Pancreatic duct secretion: control and mechanisms of transport. In: The Pancreas: Biology, Pathobiology, and Disease. V.L.W. Go, E.P. DiMagno, J.D. Gardner, E. Lebenthal, H.A. Reber, G.A. Scheele, editors. Raven Press, New York pp. 301–350.

    Google Scholar 

  • Case R.M., Harper A.A., Scratcherd T. 1968. Water and electrolyte secretion by the perfused pancreas of the cat. J. Physiol. 196:133–149

    PubMed  CAS  Google Scholar 

  • Crawford I., Maloney P.C., Zeitlin P.L., Guggino W.B., Hyde S.C., Turley H., Gatter K.C., Harris A., Higgins C.F. 1991. Immunocytochemical localization of the cystic fibrosis gene product CFTR. Proc. Nat. Acad. Sci. USA 88:9262–9266

    Article  PubMed  CAS  Google Scholar 

  • Curran P.F., MacIntosh J.R. 1962. A model system for biological water transport. Nature 193:347–348

    Article  PubMed  CAS  Google Scholar 

  • Dewhurst D.G., Hadi N.A., Hutson D., Scratcherd T. 1978. The permeability of the secretin stimulated exocrine pancreas to non-electrolytes. J. Physiol. 277:103–114

    PubMed  CAS  Google Scholar 

  • Diamond J.M. 1964. The mechanism of isotonic water transport. J. Gen. Physiol. 48:15–42

    Article  PubMed  CAS  Google Scholar 

  • Diamond J.M., Bossert W.H. 1967. Standing-gradient osmotic flow. A mechanism for coupling of water and solute transport in epithelia. J. Gen. Physiol. 50:2061–2083

    Article  PubMed  CAS  Google Scholar 

  • Fernández-Salazar M.P., Pascua P., Calvo J.J., López M.A., Case R.M., Steward M.C., San Román J.I. 2004. Basolateral anion transport mechanisms underlying fluid secretion by mouse, rat and guinea-pig pancreatic ducts. J. Physiol. 556:415–428

    Article  PubMed  CAS  Google Scholar 

  • Furuya S., Naruse S., Ko S.B.H., Ishiguro H., Yoshikawa T., Hayakawa T. 2002. Distribution of aquaporin 1 in the rat pancreatic duct system examined with light- and electron-microscopic immunohistochemistry. Cell Tissue Res. 308:75–86

    Article  PubMed  CAS  Google Scholar 

  • Gray M.A., Greenwell J.R., Argent B.E. 1988. Secretin-regulated chloride channels on the apical plasma membrane of pancreatic duct cells. J. Membrane Biol. 105:131–142

    Article  CAS  Google Scholar 

  • Gresz V., Kwon T.-H., Gong H., Agre P., Steward M.C., King L.S., Nielsen S. 2004. Immunolocalization of AQP-5 in rat parotid and submandibular salivary glands after stimulation or inhibition of secretion in vivo. Am. J. Physiol. 287:G151–G161

    CAS  Google Scholar 

  • Hill A.E. 1980. Salt-water coupling in leaky epithelia. J. Membrane Biol. 56:177–182

    Article  CAS  Google Scholar 

  • Hill A.E., Shachar-Hill B., Shachar-Hill Y. 2004. What are aquaporins for? J. Membrane Biol. 197:1–32

    Article  CAS  Google Scholar 

  • Hill A.E., Shachar-Hill B.S. 1993. A mechanism for isotonic fluid flow through the tight junctions of Necturus gallbladder epithelium. J. Membrane Biol. 136:253

    Article  CAS  Google Scholar 

  • Hurley P.T., Ferguson C.J., Kwon T.H., Andersen M.L.E., Norman A.G., Steward M.C., Nielsen S., Case R.M. 2001. Expression and immunolocalization of aquaporin water channels in rat exocrine pancreas. Am. J. Physiol. 280:G701–G709

    CAS  Google Scholar 

  • Ishibashi K., Kuwahara M., Kageyama Y., Tohsaka A., Marumo F., Sasaki S. 1997. Cloning and functional expression of a second new aquaporin abundantly expressed in testis. Biochem. Biophys. Res. Commun. 237:714–718

    Article  PubMed  CAS  Google Scholar 

  • Ishiguro H., Steward M.C., Wilson R.W., Case R.M. 1996. Bicarbonate secretion in interlobular ducts from guinea-pig pancreas. J. Physiol. 495:179–191

    PubMed  CAS  Google Scholar 

  • Jansen J.W.C.M., De Pont J.J.H.H.M., Bonting S.L. 1979. Transepithelial permeability in the rabbit pancreas. Biochim. Biophys. Acta 551:95–108

    Article  PubMed  CAS  Google Scholar 

  • King L.S., Kozono D., Agre P. 2004. From structure to disease: the evolving tale of aquaporin biology. Nature Rev. Mol. Cell Biol. 5:687–698

    Article  CAS  Google Scholar 

  • Ko S.B.H., Naruse S., Kitagawa M., Ishiguro H., Furuya S., Mizuno N., Wang Y.X., Yoshikawa T., Suzuki A., Shimano S., Hayakawa T. 2002. Aquaporins in rat pancreatic interlobular ducts. Am. J. Physiol. 282:G324–G331

    CAS  Google Scholar 

  • Koyama Y., Yamamoto T., Kondo D., Funaki H., Yaoita E., Kawasaki K., Sato N., Hatakeyama K., Kihara I. 1997. Molecular cloning of a new aquaporin from rat pancreas and liver. J. Biol. Chem. 272:30329–30333

    Article  PubMed  CAS  Google Scholar 

  • Lightwood R., Reber H.A. 1977. Micropuncture study of pancreatic secretion in the cat. Gastroenterology 72:61–66

    PubMed  CAS  Google Scholar 

  • Ma T.H., Jayaraman S., Wang K.S., Song Y.L., Yang B.X., Li J., Bastidas J.A., Verkman A.S. 2001. Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels. Am. J. Physiol. 280:C126–C134

    CAS  Google Scholar 

  • Ma T.H., Song Y.L., Gillespie A., Carlson E.J., Epstein C.J., Verkman A.S. 1999. Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels. J. Biol. Chem. 274:20071–20074

    Article  PubMed  CAS  Google Scholar 

  • Mangos J.A., McSherry N.R. 1971. Micropuncture study of the excretion of water and electrolytes by the pancreas. Am. J. Physiol. 221:496–503

    PubMed  CAS  Google Scholar 

  • Marinelli R.A., Pham L., Agre P., LaRusso N.F. 1997. Secretin promotes osmotic water transport in rat cholangiocytes by increasing aquaporin-1 water channels in plasma membrane - Evidence for a secretin-induced vesicular translocation of aquaporin-1. J. Biol. Chem. 272:12984–12988

    Article  PubMed  CAS  Google Scholar 

  • Marinelli R.A., Tietz P.S., Pham L.D., Rueckert L., Agre P., LaRusso N.F. 1999. Secretin induces the apical insertion of aquaporin-1 water channels in rat cholangiocytes. Am. J. Physiol. 276:G280–G286

    PubMed  CAS  Google Scholar 

  • Marino C.R., Matovcik L.M., Gorelick F.S., Cohn J.A. 1991. Localization of the cystic fibrosis transmembrane conductance regulator in pancreas. J. Clin. Invest. 88:712–716

    PubMed  CAS  Google Scholar 

  • Melese T., Rothman S.S. 1983. Pancreatic epithelium is permeable to sucrose and inulin across secretory cells. Proc. Nat. Acad. Sci. USA 80:4870–4874

    Article  PubMed  CAS  Google Scholar 

  • Moore M., Ma T.H., Yang B.X., Verkman A.S. 2000. Tear secretion by lacrimal glands in transgenic mice lacking water channels AQP1, AQP3, AQP4 and AQP5. Exp. Eye Res. 70:557–562

    Article  PubMed  CAS  Google Scholar 

  • Nielsen S., Smith B.L., Christensen E.I., Agre P. 1993. Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. Proc. Nat. Acad. Sci. USA 90:7275–7279

    Article  PubMed  CAS  Google Scholar 

  • Novak I., Greger R. 1988. Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane. Pfluegers Arch. 411:58–68

    Article  CAS  Google Scholar 

  • Preston G.M., Smith B.L., Zeidel M.L., Moulds J.J., Agre P. 1994. Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP water channels. Science 265:1585–1587

    PubMed  CAS  Google Scholar 

  • Roberts S.K., Yano M., Ueno Y., Pham L., Alpini G., Agre P., LaRusso N.F. 1994. Cholangiocytes express the aquaporin chip and transport water via a channel-mediated mechanism. Proc. Nat. Acad. Sci. USA 91:13009–13013

    Article  PubMed  CAS  Google Scholar 

  • Smith P.A., Sunter J.P., Case R.M. 1982. Progressive atrophy of pancreatic acinar tissue in rats fed a copper-deficient diet supplemented with D-penicillamine or triethylenetetramine: morphological and physiological studies. Digestion 23:16–30

    Article  PubMed  CAS  Google Scholar 

  • Song Y.L., Sonawane N., Verkman A.S. 2002. Localization of aquaporin-5 in sweat glands and functional analysis using knockout mice. J. Physiol. 541:561–568

    Article  PubMed  CAS  Google Scholar 

  • Song Y.L., Verkman A.S. 2001. Aquaporin-5 dependent fluid secretion in airway submucosal glands. J. Biol. Chem. 276:41288–41292

    Article  PubMed  CAS  Google Scholar 

  • Spring K.R. 1983. Fluid transport by gallbladder epithelium. J. Exp. Biol. 106:181–194

    PubMed  CAS  Google Scholar 

  • Steward M.C. 1982. Paracellular non-electrolyte permeation during fluid transport across rabbit gall-bladder epithelium. J. Physiol. 322:419–439

    PubMed  CAS  Google Scholar 

  • Steward M.C., Ishiguro H., Case R.M. 2005. Mechanisms of bicarbonate secretion in the pancreatic duct. Annu. Rev. Physiol. 67:377–409

    Article  PubMed  CAS  Google Scholar 

  • Verkman A.S. 2002. Physiological importance of aquaporin water channels. Ann. Med. 34:192–200

    PubMed  CAS  Google Scholar 

  • Whitlock R.T., Wheeler H.O. 1964. Coupled transport of solute and water across rabbit gallbladder epithelium. J. Clin. Invest. 43:2249–2265

    Article  PubMed  CAS  Google Scholar 

  • Yang B., Song Y., Zhao D., Verkman A.S. 2005. Phenotype analysis of aquaporin-8 null mice. Am. J. Physiol. 288:C1161–C1170

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Xue-Song Yang for assistance with the isolated duct permeability studies, Inger Merete Paulsen and Merete Pedersen for assistance with the immunohistochemistry, and Dr. Peter Agre for providing the AQP1 and AQP5 antibodies. The original work described here was supported by grants from the Wellcome Trust, the Cystic Fibrosis Trust (UK), the Hungarian National Scientific Research Fund (OTKA, F-049058), the Hungarian Academy of Sciences and the Danish National Research Foundation.

Author information

Authors and Affiliations

  1. Molecular Oral Biology Research Group, Department of Oral Biology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

    B. Burghardt

  2. Water and Salt Research Centre, University of Aarhus, DK-8000, Aarhus, Denmark

    S. Nielsen

  3. Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    M.C. Steward

Authors
  1. B. Burghardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M.C. Steward
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M.C. Steward.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burghardt, B., Nielsen, S. & Steward, M. The Role of Aquaporin Water Channels in Fluid Secretion by the Exocrine Pancreas. J Membrane Biol 210, 143–153 (2006). https://doi.org/10.1007/s00232-005-0852-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-005-0852-6

Keywords

Search

Navigation